Effective prevention strategies for HIV are critically needed, and an effective HIV vaccine is the best long-range hope to dramatically reduce the rate of new HIV infections. To this goal, our current understanding of the biology and epidemiology of HIV transmission remains limited. This Program Project will focus on the identification and systematic evaluation of individuals who have been recently infected with HIV and the sexual partners who transmitted HIV to them (Transmission Pairs) to elucidate and quantify epidemiologic, behavioral, biologic, virologic, and host factors that contribute to transmission. The San Diego Primary Infection research group has a long and successful history of recruiting acutely and very recently HIV-infected individuals and their transmitting partners. With new approaches to expand our identification of such study participants, as described in the Clinical and Specimen Core, we will address in Project 1 (Transmission Probability): (Aim 1) the transmission probability per contact ((J), (Aim 2) the rate of partner change (c), (Aim 3) the duration of infectious stages (D), and thus determine the reproductive number (R0) of HIV in this population. These investigations will be complemented with Project 2 (Transmission Correlates) that will identify and quantify the contributions of important biologic (Aim 1), viral (Aim 2), and host (Aim 3) correlates of HIV sexual transmission. Most importantly, this research will allow for the accurate estimation of a potential prevention strategy or candidate vaccine's anticipated efficacy based on both an estimation of the target populations'ongoing risk behavior and a thorough understanding of viral and host factors that contribute to HIV transmission. The Administrative Core (Core A) will play a central role in coordinating the administrative, fiscal, data, and statistical support for this Project as well as providing scientific support and facilitating synergistic interaction among investigators and collaborators critical to the success of the interactive projects. The Clinical and Specimen Core (Core B) will identify, recruit and enroll study subjects and collect, process, store, and manage the clinical specimens needed to meet the objectives of the two proposed research projects. PROJECT 1: Transmission Probability (Strathdee, S.) PROJECT 1 DESCRIPTION (provided by applicant): Modeling prevention interventions requires insights into epidemiological and biological factors affecting HIV transmission. Project 1 of the proposed Program Project addresses the epidemiological determinants of HIV transmission by examining the per contact transmission probability (P), the rate of partner change/ contact rate (c), and the duration of infectiousness (D), which all contribute to the reproductive number (R0= pcD), defined as the average number of secondary infections arising from a single infection in a completely susceptible population. To achieve this objective, we will address the following specific aims: Aim 1: Per contact transmission probability (P) - The per contact sexual transmission probability of HIV will be estimated, taking into account stage of HIV infection in the source partner, presence of viral and bacterial sexually transmitted infections, circumcision status, and other biological cofactors investigated in Project 2. The absolute and relative difference of transmission probability for insertive versus receptive anal sex will also be considered. Aim 2: Rate of partner change (c) - The role of partner selection in HIV acquisition and transmission risk will be examined at individual, partnership, and network levels. At the individual level, the relative contribution of HIV risk due to number of sexual acts versus number of sexual partners will be examined. At the partnership level, risk characteristics will be compared between transmitting and seroconcordant non-transmitting partnerships. At the network level, risk of acquisition and transmission of HIV based on the location of individuals within networks of venues used to meet sex partners, and correlates of being in a transmission cluster, will be elucidated. Aim 3: Duration of infectiousness (D) - To determine how duration of the infectious stages of HIV infection intersects with risk behaviors and time to antiretroviral treatment. We will use data from Aims 1-3 to develop a stochastic, individual-based model to predict the number of secondary infections arising from individuals diagnosed during recent HIV infection as they transit to chronic infection, and the potential impact of short-course antiviral therapy on reducing transmission. Project 1 depends on well-characterized clinical data and specimens collected by the Clinical and Specimen Core and the subsequent measurement of transmission correlates in Project 2. Epidemiological data contributing to HIV transmission collected in Project 1 will help to define correlates of HIV transmission in Project 2. The Administrative Core will coordinate administrative, fiscal, data, and statistical support for Projects 1 and 2. These data will provide critical information on epidemiological determinants of HIV transmission in a setting where HIV-1 subtype B predominates, which are lacking for MSM, and will generate important exploratory data for other populations.